A system for the large scale, dynamic quantification of transcription factor activity was applied to investigate the mechanism of action for PARP inhibitors. Of the 34 TFs investigated, 15 had differential activity in the presence of the PARP inhibitor olaparib. A few of the TF had differential activity in BRCA1-wild type and BRCA1-null cells. This differential activity may underlie why some patients respond whereas others are resistant. In addition, five PARP-1 inhibitor resistant clones were established from BRCA1-null type cells. Cell array analysis from these clones will provide us valuable insights into addressing the occurrence of resistance. We are continuing to investigate these factors to identify whether targeting these additional pathways can increase the efficacy or reduce resistance to PARP inhibitors.
